Naturally Existing Oncolytic Virus M1 Is Nonpathogenic for the Nonhuman Primates after Multiple Rounds of Repeated Intravenous Injections

Haipeng Zhang, Yuan Lin, Kai Li, Jiankai Liang, Xiao Xiao, Jing Cai, Yaqian Tan, Fan Xing, Jialuo Mai, Yuan Li, Wenli Chen, Longxiang Sheng, Jiayu Gu, Wenbo Zhu, Wei Yin, Pengxin Qiu, Xingwen Su, Bingzheng Lu, Xuyan Tian, Jinhui LiuWanjun Lu, Yunling Dou, Yijun Huang, Bing Hu, Zhuang Kang, Guangping Gao, Zixu Mao, Shi Yuan Cheng, Ling Lu, Xue Tao Bai, Shoufang Gong, Guangmei Yan, Jun Hu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Cancers figure among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next 2 decades. Development of novel therapeutic agents is urgently needed for clinical cancer therapy. Alphavirus M1 is a Getah-like virus isolated from China with a genome of positive single-strand RNA. We have previously identified that alphavirus M1 is a naturally existing oncolytic virus with significant anticancer activity against different kinds of cancer (e.g., liver cancer, bladder cancer, and colon cancer). To support the incoming clinical trial of intravenous administration of alphavirus M1 to cancer patients, we assessed the safety of M1 in adult nonhuman primates. We previously presented the genome sequencing data of the cynomolgus macaques (Macaca fascicularis), which was demonstrated as an ideal animal species for virus infection study. Therefore, we chose cynomolgus macaques of either sex for the present safety study of oncolytic virus M1. In the first round of administration, five experimental macaques were intravenously injected with six times of oncolytic virus M1 (1 × 109 pfu/dose) in 1 week, compared with five vehicle-injected control animals. The last two rounds of injections were further completed in the following months in the same way as the first round. Body weight, temperature, complete blood count, clinical biochemistries, cytokine profiles, lymphocytes subsets, neutralizing antibody, and clinical symptoms were closely monitored at different time points. Magnetic resonance imaging was also performed to assess the possibility of encephalitis or arthritis. As a result, no clinical, biochemical, immunological, or medical imaging or other pathological evidence of toxicity was found during the whole process of the study. Our results in cynomolgus macaques suggested the safety of intravenous administration of oncolytic virus M1 in cancer patients in the future.

Original languageEnglish (US)
Pages (from-to)700-711
Number of pages12
JournalHuman Gene Therapy
Volume27
Issue number9
DOIs
StatePublished - Sep 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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